Neuromodulation provides a mechanism whereby the nervous system can expand the range of both its responsiveness to afferent signals and its repertoire of efferent responses. Modulation of both input and output properties of the nervous system significantly contributes to the complexity of mammalian behavior. The primary goal of this research project is to use the vasopressin (AVP) neuromodulation of norepinephrine (NE)-induced accumulation of cAMP interaction in the hippocampus as neuromodulatory model to test the hypothesis that in some instances neuromodulatory can serve as a biochemical analog of the associative processes which appear to govern learning and memory. If this postulate is true, then the factors which govern electrophysiological associative processes, namely long-term potentiation, should also hold true for the biochemical analog. To test this hypothesis, five specific aims related to associative processes will be determined over a five year period: (1) Determination of the anatomical and spatial relationship between recognition sites for AVP and NE in the hippocampus? (2) Determination of the temporal relationship between activation of receptors for AVP and NE and the subsequent expression of neuromodulation? (3) Determination of the mechanism underlying the calcium/calmodulin dependency of AVP-induced neuromodulation? (4) Determination of the influence of AVP and NE singly and in combination on the induction of long-term potentiation in the dentate gyrus of the hippocampus? (5) Determination of the effect of AVP and NE singly and in combination on the growth and morphology of cultured hippocampal and dentate gyrus neurons. Information derived from this project will lead to insights which will have significance from basic science, theorectical and applied perspectives.